The invention relates generally to the field of endoscopic imaging and more specifically, to the field of optical design of compact high collection power endoscopic objectives for fluorescence and white light imaging.
Fluorescence imaging is used to highlight molecules and structures not otherwise visible under white light illumination. By administering a molecular contrast agent to a patient, disease processes can be specifically labeled for visualization during clinical examination. In concert with white light imaging, fluorescence imaging captures movies of anatomy with tissue specific information, and provides the clinician with a macroscopic visualization of biology in its intact and native physiological state. It holds promise as a way for real time guidance for tumor resection, sentinel lymph node mapping, vasculature and tissue perfusion imaging, as well as early detection of colorectal cancer.
However, many technical challenges are still present. One of the challenges is the specificity and affinity of the contrast agent. With respect to the physics of imaging, a challenge is light attenuation in living tissue. Yet another challenge is the sensitivity of the imaging instrument at low light conditions.
Light attenuation in tissue, is related to the spectroscopic properties of the biological medium and the optical properties of the fluorescent contrast agent, or fluorophore. Shifting the emission wavelength of the fluorophore from the visible to the deep red or near infrared (NIR) improves visualization by providing better rejection of ambient light and deeper penetration depth into tissue. For example, in addition to water, the tissue constituents that dominate absorption of light in the visible and NIR are hemoglobin, bilirubin, and lipids, which have absorption minima in the red to NIR. Moreover, there is a substantial decrease in tissue scattering in the NIR relative to visible wavelengths. The reduced absorption and scattering (collectively known as the attenuation coefficient) results in less light attenuation and thus deeper penetration. Imaging in the NIR minimizes background autofluorescence, as most of the endogenous fluorescent species (e.g., collagen, elastin, NAD(P)H) emit in the visible spectrum.
The required sensitivity of the system depends on whether a targeted or non-targeted agent is used. Some clinical procedures do not require specific molecular targeting. For example, during cholecystectomy, an uncommon but potentially serious complication with the procedure is injury to the common bile duct. For this application, a targeted contrast agent, such as methylene blue, can be used to highlight the bile duct to give the surgeon guidance during the procedure. Such agents can be introduced with relatively high concentration, and are not limited by the local update of the dye. Other non-targeted applications include sentinel lymph node mapping, and highlighting of vasculature and tissue perfusion.
However, imaging of targeted agents, requires higher sensitivity to detect low levels of the agent. Regardless of the dose orally, intravascularly, or otherwise administered to the patient, local concentrations of the contrast agent can be on the order of tens of nmol/L.
The imaging instrument sensitivity is determined by collection efficiency, illumination power density at the sample, and detector sensitivity. The entrance pupil diameter (EPD) of the primary optics, which determines the numerical aperture (NA), impacts collection efficiency. In an endoscopic imaging system, the EPD is normally 0.2 mm. At 25-100 mm working distance, the NA may be on the order of 0.002-0.008, resulting in low collection power. The illumination power can be partially increased to compensate for that loss in collection efficiency, but only up to the point of maximum permissible exposure (MPE), dictated by ANSI-Z-136.1. Another practical consideration is limiting the excitation light source to a Class III device (<500 mW exposure in the NIR) to avoid the use of laser interlocks and personal protective equipment. However, to illuminate a wide field of view of 120°, the irradiance at the sample provided by a Class III excitation source can be very low (<2.5 mW/cm2). On the detector side, the majority of video endoscopes use ¼ inch or ⅙ inch detectors, which have small pixels, resulting in very low sensitivity.
Conventional endoscope objectives use a retrofocus objective designed to cover large fields of view (FOV). Generally, a small entrance pupil diameter (EPD) is used to maintain large depth of field, and to reduce aberrations at large field. Although this is normally adequate for white light imaging, it is not optimized for fluorescence imaging, where the typical fluorescence signal strength from stained tissue is substantially weaker than the white light reflectance image. It is advantageous for an objective intended for dual use of white light and fluorescence imaging to improve collection power, while maintaining a small overall diameter, large FOV, and high optical resolution for both visible and near infrared wavelengths.
It is therefore desirable to provide a compact endoscope objective with high collection power for multi-mode endoscope systems.